CN110596107A - Reusable high-flux terahertz metamaterial rapid detection method - Google Patents
Reusable high-flux terahertz metamaterial rapid detection method Download PDFInfo
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Abstract
The invention discloses a reusable high-flux terahertz metamaterial rapid detection method, which comprises the steps of firstly, obtaining an object to be detected and placing the object on a metamaterial chip; if the diameter of the object to be detected is large, removing solvent water molecules in the object to be detected by adopting a filtering membrane; if the size of the sample is small, adding magnetic beads with capture probes into the sample, and separating solvent water molecules of the sample in a magnetic attraction manner to enable the sample to be deposited on the surface of the metamaterial chip; then the metamaterial chip is sent to a human detection instrument to respectively detect the objects to be detected in different detection areas; and finally, detecting the objects to be detected on all detection areas on the metamaterial chip. The method provided by the invention quickly separates the substance to be detected and the solvent water by combining magnetic attraction with a filtering membrane, simultaneously realizes high-flux detection of a plurality of detection areas on a high-precision array type mobile carrier, and realizes the reusability of the metamaterial chip by adopting a biological enzyme-sodium dodecyl sulfate-isopropanol triple cleaning method after the detection.
Description
Technical Field
The invention relates to the technical field of sensors, in particular to a reusable high-flux terahertz metamaterial rapid detection method.
Background
Terahertz (THz) metamaterial refers to a novel artificial material which interacts with the Terahertz metamaterial to form THz waveband electromagnetic waves, and can flexibly control physical parameters such as amplitude, phase and the like of the THz waves. The strong local field distribution and the high Q value resonance of the metamaterial make the metamaterial very sensitive to substances attached to the surface of the metamaterial, and after the surface of the metamaterial is covered with the substances or the substances are changed, the change of the local effective dielectric constant of the metamaterial can cause the change of capacitance, so that the resonant frequency of the metamaterial is changed. Therefore, the detection of the trace sample can be realized by detecting the displacement of the resonance frequency of the metamaterial.
As a novel sensing mode, the THz metamaterial technology is widely applied to a plurality of fields such as semiconductor materials, electronic devices, chemical substances, biomedical treatment and the like at present, but when the THz metamaterial is used for detecting samples, particularly liquid samples, the THz metamaterial technology also has the following steps in the processes of detection, detection and detection: long preparation time, low detection flux and poor reusability.
1. The preparation time is long: at present, the types of samples which can be detected by the metamaterial are various, but when the detection of the liquid sample is related, the method basically comprises the steps of firstly dripping the liquid sample on the surface of the metamaterial, and after the liquid sample is dried, closely combining a substance to be detected with the surface structure of the metamaterial and then measuring. The main reason is that the metamaterial only generates signal response to substances near the structure of the metamaterial, and the object to be measured in the liquid sample is in a suspension state, so that a larger distance still exists between the object to be measured and the metamaterial structure after the object to be measured is dripped on the surface of the metamaterial. Therefore, the traditional method adopts a drying mode to remove the solvent water, so that the substance to be detected is deposited on the surface structure of the metamaterial. But in order not to damage the structure, the drying temperature is generally less than 70 ℃, so the whole preparation link is generally as long as 20-30 minutes, and the detection time is greatly consumed.
2. The detection flux is low: in order to ensure that the metamaterial position and the THz wave spot position are fixed in the detection process, only one chip is mostly placed on the conventional metamaterial detection device, and only one sample can be detected at one time after long-time preparation in the early stage. The low-flux detection mode greatly improves the detection time and the value cost and reduces the detection efficiency.
3. Poor reusability: after detection is finished, substances deposited on the surface of the metamaterial structure can be tightly combined with the surface of the metamaterial due to loss of moisture and electrostatic adsorption, and the traditional water washing method cannot achieve the effect of removing residual substances, so that the reusability of the metamaterial is poor.
Disclosure of Invention
In view of this, the present invention provides a reusable method for rapidly detecting a high-flux terahertz metamaterial.
In order to achieve the purpose, the invention provides the following technical scheme:
the reusable high-flux terahertz metamaterial rapid detection method provided by the technical scheme comprises the following steps:
obtaining an object to be detected and placing the object to be detected on a detection area of the metamaterial chip;
judging whether the diameter of the object to be detected exceeds a preset value, if so, removing solvent water molecules in the object to be detected by adopting a filtering membrane; arranging a filtering membrane matched with the metamaterial chip above the object to be detected, and extruding the object to be detected from top to bottom by the filtering membrane; removing solvent water molecules above the filtering membrane until the object to be detected is deposited on the surface of the metamaterial chip;
if not, adding magnetic beads with capture probes into the object to be detected, capturing the object to be detected on the surfaces of the magnetic beads, then arranging a magnetic material layer below the metamaterial chip, and separating solvent water molecules of the object to be detected in a magnetic attraction manner to enable the object to be detected to be deposited on the surfaces of the metamaterial chip;
sending the metamaterial chip to a detection instrument to respectively detect objects to be detected in different detection areas;
and (4) until the objects to be detected on all detection areas on the metamaterial chip are detected.
Further, the method also comprises the following steps:
the metamaterial chip after detection is cleaned by adopting a bio-enzyme-SDS-isopropanol triple method, and the method comprises the following specific steps:
placing the metamaterial chip in SDS solution for soaking; removing the electrostatic attraction around the magnetic beads and the object to be detected;
washing the surface of the metamaterial chip by using deionized water;
the metamaterial chips were rinsed with isopropanol and blown dry with nitrogen.
Further, the method also comprises the following steps:
the bio-enzyme solution is applied on the surface of the metamaterial chip before soaking with the SDS solution.
Further, the filter membrane is used for filtering the object to be measured with the diameter of 0.5-0.8 μm.
Furthermore, the filtering pore diameter arranged on the filtering membrane is 0.22-0.4 μm.
Furthermore, the particle size of the magnetic bead is 0.22-1.0 μm.
Further, the metamaterial chip is arranged on an object stage by adopting an array moving structure, and the object stage comprises a base;
the base is provided with a positioning groove; the metamaterial chip is movably arranged in the positioning groove;
the metamaterial chip is provided with a plurality of detection areas for placing objects to be detected;
the base is provided with a light hole, and the light hole is matched with a detection area on the metamaterial chip so as to be suitable for the interaction between the terahertz waves and an object to be detected on the detection area of the metamaterial chip; the magnetic material layer is arranged between the positioning groove and the metamaterial chip, so that the metamaterial chip is positioned in the positioning groove through magnetic attraction, the magnetic material layer comprises a first magnetic material layer and a second magnetic material layer, the first magnetic material layer is arranged on the positioning groove, the second magnetic material layer is arranged on the metamaterial chip, and magnetic force can be generated between the first magnetic material layer and the second magnetic material layer.
Furthermore, the objective table also comprises a carrier which is movably arranged on the base; the metamaterial chip is arranged on the carrier;
a positioning shaft is arranged below the carrier and matched with a groove formed in the base, and the positioning shaft and the groove are movably connected so as to be suitable for interaction between the terahertz waves and the object to be detected on the metamaterial chip detection area.
Further, the carrier is a mobile carrier, and the mobile carrier comprises a main body, a to-be-detected part and a detection part; the detection part is arranged at the periphery of the main body, the detection part is arranged in the middle of the main body, a channel for the metamaterial chip to slide is arranged between the detection part and the detection part, and the detection part is right above the light transmission hole so as to be suitable for the interaction between the terahertz waves and the object to be detected on the detection part of the metamaterial chip;
the main part is the circular slab, wait to examine a portion and set up along the circumference, the detection portion sets up in the centre of a circle, the passageway is for setting up the recess between waiting to examine a portion and the detection portion, metamaterial chip and recess cooperation are so that the metamaterial chip can remove on the recess.
Further, the detection of the object to be detected in the metamaterial chip human-sending detection instrument is realized according to the following steps:
placing the object stage on an object stage fixing support in the detection instrument;
adjusting a light transmission hole of the objective table to enable the terahertz waves to act on an object to be detected on the detection area of the metamaterial chip;
rotating the carrier on the objective table after the detection of the area to be detected is finished;
adjusting the position of the next detection area of the metamaterial chip on the carrier;
so that the position of the next detection area is right opposite to the light-transmitting hole of the objective table;
until all detection areas on the metamaterial chip are detected.
The device provided by the invention has the following beneficial effects that:
(1) the detection method has the characteristics of rapidness in the detection process: the device adopts a mode of combining the filtration membrane and the magnetic attraction of the object to be tested to remove the solvent water in the liquid sample, the object to be tested is deposited on the surface of the metamaterial structure, the traditional long-time drying method is abandoned, and compared with the traditional drying process, the sample preparation time is greatly shortened. Meanwhile, the metamaterial chip is distributed in various arrays, and the pretreatment operations before simultaneous acquisition and detection of a plurality of detection samples, such as simultaneous drying of a plurality of samples and the like, can be realized respectively through the rapid matching of the carrier and the base; meanwhile, the magnetic material layer between the carrier positioning shaft and the base groove is matched and connected, the position of the metamaterial chip is accurately positioned under the action of magnetic attraction, the time for replacing a sample in the detection process is greatly saved, and the rapid detection process of the terahertz metamaterial is realized.
(2) The detection method has the characteristics of mass detection process: the high-precision array type mobile carrier is adopted, the array type metamaterial chip is arranged on the carrier, and the rotation and the sliding are realized under the action of the magnetic material layer by combining the positioning shaft and the groove, so that the rapid switching and the batch detection of a plurality of samples can be realized, and the high-flux detection mode of the terahertz metamaterial can be realized.
(3) The detection chip of the detection method has the characteristics of repeatability: after the metamaterial chip in the device is used, a biological enzyme-SDS-isopropanol triple cleaning method is adopted, so that the electrostatic attraction around the magnetic beads and the sample to be detected can be effectively removed, the bonding force between the magnetic beads and the metamaterial chip is reduced, and the residual substance to be detected is cleaned by deionized water washing and isopropanol washing.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention. The objectives and other advantages of the invention may be realized and attained by the means of the instrumentalities and combinations particularly pointed out hereinafter.
Drawings
In order to make the object, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings for explanation:
FIG. 1 is a flow chart of a reusable high-flux terahertz metamaterial rapid detection method.
FIG. 2 is a schematic view of the overall structure of the detecting device with a magnetic layer disposed in a positioning groove.
Fig. 3 is a schematic view of a matching structure of the carrier and the base.
Fig. 4 is a schematic structural view of the mobile carrier.
FIG. 5 is a schematic view of a groove-type detecting device.
FIG. 6 is a schematic structural diagram of a four-chip detection device.
FIG. 7 is a schematic structural diagram of a detecting device with nine chip arrays.
Fig. 8 is a schematic view of a protrusion and a groove structure between the base and the carrier.
FIG. 9 is a schematic diagram showing the positions of the formants after the metamaterial chip is cleaned by the triple method and the common method.
In the figure, 1 is a base, 11 is a positioning groove, 12 is a light hole, 21 is a carrier, and 22 is a chip; 23 is a projection, 3 is a detection area, 4 is a magnetic material layer, and 5 is a filter membrane;
24 is a groove; 241 is an X-direction groove, 242 is a Y-direction groove; 25 is a positioning shaft; 26 is a positioning device; 27 is a pushing boss; 211 is a positioning hole, 212 is a positioning projection.
Reference numeral 31 denotes a main body, 32 denotes a to-be-detected portion, and 33 denotes a detection portion; 34 are channels.
Detailed Description
The present invention is further described with reference to the following drawings and specific examples so that those skilled in the art can better understand the present invention and can practice the present invention, but the examples are not intended to limit the present invention.
Example 1
As shown in fig. 1, the reusable high-flux terahertz metamaterial rapid detection apparatus and method provided in this embodiment include the following steps:
obtaining an object to be detected and placing the object to be detected on a detection area of the metamaterial chip;
judging whether the diameter of the object to be detected exceeds a preset value, if so, removing solvent water molecules in the object to be detected by adopting a filtering membrane; arranging a filtering membrane matched with the metamaterial chip above the object to be detected, and extruding the object to be detected from top to bottom by the filtering membrane; removing solvent water molecules above the filtering membrane until the object to be detected is deposited on the surface of the metamaterial chip;
if not, adding magnetic beads with capture probes into the object to be detected, capturing the object to be detected on the surfaces of the magnetic beads, then arranging a magnetic material layer below the metamaterial chip, and separating solvent water molecules of the object to be detected in a magnetic attraction manner to enable the object to be detected to be deposited on the surfaces of the metamaterial chip;
sending the metamaterial chip to a detection instrument to respectively detect objects to be detected in different detection areas; the method is realized by the following steps:
placing the object stage on an object stage fixing support in the detection instrument;
adjusting a light transmission hole of the objective table to enable the terahertz waves to act on an object to be detected on the detection area of the metamaterial chip;
rotating the carrier on the objective table after the detection of the area to be detected is finished;
adjusting the position of the next detection area of the metamaterial chip on the carrier;
so that the position of the next detection area is right opposite to the light-transmitting hole of the objective table;
until all detection areas on the metamaterial chip are detected.
Until the objects to be detected on all detection areas on the metamaterial chip are detected;
the metamaterial chip after detection is cleaned by adopting a bio-enzyme-SDS-isopropanol triple method, and the method comprises the following specific steps:
applying a biological enzyme solution on the surface of the metamaterial chip;
placing the metamaterial chip in SDS solution for soaking; removing the electrostatic attraction around the magnetic beads and the object to be detected;
washing the surface of the metamaterial chip by using deionized water;
the metamaterial chips were rinsed with isopropanol and blown dry with nitrogen.
The filtering membrane provided by the embodiment is used for filtering an object to be detected with a diameter of 0.5 to 0.8 μm, and the preset value of the diameter of the object to be detected in the embodiment is 0.5 μm;
the filtration pore diameter arranged on the filtration membrane provided by the embodiment is 0.22-0.4 μm, and the filtration membrane is made of PVC material.
The magnetic bead provided by the embodiment has a particle size of 0.22-1.0 μm, and is used for capturing an object to be detected with a diameter of 0.2 μm to 0.5 μm on the surface of the magnetic bead, and under the magnetic force action of a magnetic material layer arranged below the metamaterial chip, the object to be detected and solvent water are separated, so that the object to be detected is deposited on the surface of the metamaterial chip.
The method provided by the embodiment quickly separates the substance to be detected and the solvent water by combining magnetic attraction with a filtering membrane, simultaneously realizes high-flux detection of a plurality of detection areas on a high-precision array type mobile carrier, and realizes the reusability of the metamaterial chip by adopting a biological enzyme-Sodium Dodecyl Sulfate (SDS) -isopropanol triple washing method after the detection.
Wherein, magnetic attraction is combined with a filtration membrane: the traditional long-time drying method is abandoned, and the purposes of removing the solvent water in the liquid sample and depositing the substance to be detected on the surface of the metamaterial structure are achieved by adopting a magnetic attraction and filtration combined mode. The specific process is as follows: aiming at the situation that the diameter of a substance to be detected in a liquid sample is larger than 0.5 mu m (such as viruses, bacteria, cells and the like), a filtering membrane device (the material can be high-strength PVC and the like) with the same size as the chip and the pore diameter of 0.22 mu m is arranged above a metamaterial chip structure, the liquid sample is firstly dripped on the surface of the metamaterial, then the filtering membrane is used for extruding the liquid sample from top to bottom, and the substance to be detected with the diameter larger than the pore diameter of the filtering membrane can be extruded on the metamaterial structure, and solvent water molecules are filtered on the filtering membrane and can be easily wiped away. Most of substances to be detected can be deposited on the surface of the metamaterial structure after 3-5 times of filtration. And aiming at the condition that the diameter of the substance to be detected in the liquid sample is less than 0.5 mu m (such as chemical substances, proteins, nucleic acids, salt ions and the like), firstly adding magnetic beads with specific capture probes into the sample, capturing the substance to be detected on the surfaces of the magnetic beads, then arranging a magnet layer below the metamaterial structure, and separating the substance to be detected and solvent water by adopting a magnetic attraction mode so that the substance to be detected is deposited on the surface of the metamaterial. In the method, the filtering process of the filter membrane only needs 1 minute, and the process of magnetically separating the substance to be detected only needs 5 minutes, so that the sample preparation time is greatly shortened compared with the traditional drying process.
The embodiment adopts a high-precision array type mobile carrier: the metamaterial chip is designed into a 3 x 3 array or other specifications, and a corresponding chip carrier and a base are designed, wherein a positioning shaft is arranged below the carrier, and a positioning groove is arranged on the base. The positioning shaft on the carrier is connected with the groove in a matched mode, the positioning shaft and the groove are made of ferromagnetic materials, the position of the chip is accurately positioned in a magnetic attraction mode, the carrier can slide in the groove by the aid of the positioning shaft, and the chip is accurately positioned in a magnetic attraction mode, so that the detection area of the chip is always coincided with the light spot position of the THz wave. The module can realize the rapid switching and batch detection of a plurality of samples by arranging the array chip and positioning the shaft sliding mode, and greatly improves the flux of metamaterial detection.
Example 2
As shown in fig. 2, the metamaterial chip provided in this embodiment is disposed on an object stage by using an array moving structure, where the object stage includes a base; the base is provided with a positioning groove; the metamaterial chip is movably arranged in the positioning groove; the metamaterial chip is provided with a plurality of detection areas for placing objects to be detected; the base is provided with a light hole, and the light hole is matched with a detection area on the metamaterial chip so as to be suitable for the interaction between the terahertz waves and an object to be detected on the detection area of the metamaterial chip; the magnetic material layer is arranged between the positioning groove and the metamaterial chip, so that the metamaterial chip is positioned in the positioning groove through magnetic attraction, the magnetic material layer comprises a first magnetic material layer and a second magnetic material layer, the first magnetic material layer is arranged on the positioning groove, the second magnetic material layer is arranged on the metamaterial chip, and magnetic force can be generated between the first magnetic material layer and the second magnetic material layer.
The objective table further comprises a carrier, and the carrier is movably arranged on the base; the metamaterial chip is arranged on the carrier; a positioning shaft is arranged below the carrier and matched with a groove formed in the base, and the positioning shaft and the groove are movably connected so as to be suitable for interaction between the terahertz waves and the object to be detected on the metamaterial chip detection area.
The carrier is a mobile carrier, and the mobile carrier comprises a main body, a to-be-detected part and a detection part; the detection part is arranged at the periphery of the main body, the detection part is arranged in the middle of the main body, a channel for the metamaterial chip to slide is arranged between the detection part and the detection part, and the detection part is right above the light transmission hole so as to be suitable for the interaction between the terahertz waves and the object to be detected on the detection part of the metamaterial chip;
the main part is the circular slab, wait to examine a portion and set up along the circumference, the detection portion sets up in the centre of a circle, the passageway is for setting up the recess between waiting to examine a portion and the detection portion, metamaterial chip and recess cooperation are so that the metamaterial chip can remove on the recess.
As shown in fig. 3, the carrier provided in this embodiment is movably disposed on the base; the chip is arranged on the carrier. The terahertz wave detection device is characterized in that a positioning shaft is arranged below the carrier, the positioning shaft is matched with a groove arranged on the base, and the positioning shaft and the groove are movably connected so as to be suitable for determining that terahertz waves passing through the light hole act on an object to be detected in a corresponding detection area on the chip.
A magnetic material layer capable of generating attraction is arranged between the positioning shaft and the groove, so that the positioning shaft is suitable for being attracted and positioned through magnetic force when moving in the positioning groove, and the detection area of the chip is always coincided with the position of a light spot of the terahertz wave.
The base of the detection device provided by this embodiment is further provided with a positioning groove, the positioning groove is a V-shaped groove and is used for determining the position of the chip, and the V-shaped groove comprises an X-direction groove and a Y-direction groove; the X-direction groove is provided with three parallel X-direction grooves, and the Y-direction positioning groove is provided with three parallel Y-direction grooves.
As shown in fig. 4, the carrier in the detection apparatus provided in this embodiment is a mobile carrier, and the mobile carrier includes a main body, a to-be-detected portion, and a detection portion; wait to examine a portion and set up around the main part, the detection part sets up in the main part middle part, it is used for the gliding passageway of chip to wait to be provided with between portion and the detection part, the detection part just to the light trap top to be suitable for the terahertz wave through the light trap to act on the detection part.
The main part is circular platelike, wait to examine the portion and set up along the circumference, the detection part sets up in the centre of a circle, the passageway is for setting up the recess between waiting to examine portion and the detection part, the recess.
As shown in fig. 5, the carrier provided in this embodiment is a circular carrier, and the circular carrier is provided with an array chip;
a positioning device is arranged between the circular carrier and the positioning groove, and the positioning device gradually changes the position of the circular carrier under the action of external force, so that each chip in the array chips is positioned at the light-transmitting hole, and the terahertz waves passing through the light-transmitting holes act on the corresponding chip;
as shown in fig. 6, 7 and 8, the carrier provided in the present embodiment is a rectangular carrier, and the rectangular carrier is provided with an array chip; a positioning device is arranged between the rectangular carrier and the positioning groove, and the positioning device gradually changes the position of the rectangular carrier under the action of external force, so that each chip in the array chips is positioned at the light-transmitting hole, and the terahertz waves passing through the light-transmitting holes act on the corresponding chip; the positioning device comprises a positioning hole and a positioning bulge; the positioning hole is arranged in the positioning groove, the positioning bulge is arranged on the carrier, and the positioning hole and the positioning bulge are matched to fix the position of the carrier.
The carrier and the chip in the detection device provided by the embodiment are used as an object stage of an object to be detected, and the object stage is placed in the positioning groove; the object stage is arranged in the positioning groove in a non-fixed mode; when the position of the object stage needs to be adjusted, the object stage can be placed in the positioning groove again according to the required position direction, and therefore the object stage is movably connected with the base.
As shown in fig. 6, the four detection areas are arranged in the figure, each detection area is a chip provided with an object to be detected, the carrier is a rectangular carrier, and the rectangular carrier is provided with an array chip;
the positioning device is arranged between the rectangular carrier and the positioning groove and adopts a buckle type, the buckle type positioning device comprises a convex part arranged on the positioning groove and a concave part arranged on the carrier, a pushing boss is further arranged on the carrier, when the carrier needs to be rotated, external force is applied to the pushing boss, the position of the rectangular carrier is gradually changed under the action of the external force, the rectangular carrier is fixed through the positioning device, the convex part and the concave part are combined together in a buckle mode, the rectangular carrier is fixed at a new position, each chip in the array type chips is located at the light transmitting hole, and terahertz waves suitable for passing through the light transmitting holes act on the corresponding chip.
As shown in fig. 5, the carrier is a circular carrier, and nine chips are arranged on the circular carrier and distributed in an array form; a positioning device is arranged between the circular carrier and the positioning groove and comprises a positioning hole and a positioning bulge; the positioning hole is arranged in the positioning groove, the positioning bulge is arranged on the carrier, and the positioning hole and the positioning bulge are matched for fixing the position of the carrier; the carrier is further provided with a pushing boss, when the carrier needs to be rotated, external force is applied to the pushing boss, the position of the rectangular carrier is gradually changed under the action of the external force, and the rectangular carrier is fixed through the positioning device, so that each chip in the array chips is located at the light transmitting hole, and terahertz waves which pass through the light transmitting holes act on the corresponding chip.
The groove provided by the embodiment is a V-shaped groove and is used for determining the position of a chip, and the V-shaped groove comprises an X-direction groove and a Y-direction groove; when moving, the objective table needs to be lifted, and each test position is reached through the combination of the X-direction groove and the Y-direction groove; the X-direction groove of the present embodiment may be three X-direction grooves arranged in parallel to each other, and the Y-direction groove may be three Y-direction grooves arranged in parallel to each other. The protruding structure matched with the V-shaped groove and arranged on the carrier is shown in fig. 6 and 7, wherein the protruding portion is a triangular protrusion matched with the V-shaped grooves in different directions.
The chips are high-flux chips, and the chips are arranged according to a preset spacing distance. The high-flux chip comprises a plurality of metamaterial chips arranged according to an array structure; a single metamaterial chip is arranged between each metamaterial chip according to a preset spacing distance; each sample is kept at a distance to prevent contamination of the sample.
The stage of this embodiment can be fabricated as a 3 x 3, 6 x 6 or 9 x 9 array, or as an array required in other practical cases, and a metamaterial chip is placed on each array unit of the stage, for example, the stage of the 3 x 3 array is used in cooperation with a base, and 9 samples can be detected at a time by moving the stage to achieve the purpose of detecting 9 different regions. When the device is used for detection, 9 samples can be added once and dried together, and then THz detection can quickly obtain signals of the 9 samples only by moving the objective table, so that the time is saved. In the detection process, the problem that nucleic acid remains on the metamaterial after detection can be solved by adopting a biological + physical combined method: firstly, adding endonuclease for incubation at 37 ℃ for 5min to degrade nucleic acid fragments; then washing with deionized water for 2 min; and finally, washing with isopropanol for 2min, and drying with nitrogen. Because the endonuclease can degrade the nucleic acid in small segments, the nucleic acid is more easily dissolved in water; however, isopropanol is highly volatile and can take away residual substances in the process.
As shown in fig. 9, fig. 9 is a schematic diagram of the position of a resonance peak after a metamaterial chip is cleaned by a triple method and a common method, in the bio-enzyme-SDS-isopropanol triple cleaning method provided in this embodiment, after detection is completed, the metamaterial chip is first placed in a 0.01% SDS solution to be soaked for 5min, and SDS is an anionic surfactant, and can effectively remove electrostatic attraction around magnetic beads and a sample to be detected, and reduce the binding force between the magnetic beads and a metamaterial structure. Then wash chip surface 2min with the deionized water, wash 2min with isopropanol at last, nitrogen gas weathers can, because isopropanol has strong volatility, the process of weathering can take away remaining material to be measured in the lump, and concrete step is as follows:
1. placing the metamaterial chip in 0.01% SDS solution to soak for 5min, and removing the magnetic beads on the chip and the electrostatic attraction around the object to be detected;
2. washing the surface of the metamaterial chip for at least 2min by using deionized water at the flow rate of 200 ml/min;
3. and (3) flushing the surface of the metamaterial chip with isopropanol at the flow rate of 200ml/min for at least 2min, and drying with nitrogen.
4. The washing of special biological samples such as nucleic acid protein cells can increase the degradation process of biological enzyme solutions such as endonuclease, protease, pancreatin and the like, and the specific implementation mode is as follows: firstly, dropping a biological enzyme solution on the surface of a chip structure (wherein 5 muL of Benzonase nucleic acid high-activity totipotent Nuclease which is more than or equal to 250U/muL is adopted for a nucleic acid sample, 5 muL of anzyme proteolytic enzyme is adopted for a protein sample, and 0.5% of pancreatic enzyme of Gibco is adopted for a cell sample), incubating for 5-10min at 37 ℃, repeating for 3 times, and then cleaning according to the method.
As shown in fig. 9, the curves are sequentially arranged from top to bottom according to the curve intersecting the left ordinate axis, and the curves in the figure are respectively marked as a first curve, a second curve, a third curve and a fourth curve; wherein, the first curve is a blank metamaterial without being cleaned; the second curve represents the schematic position diagram of the formants after the triple washing, and the third curve represents the schematic position diagram of the formants after the common washing; the fourth curve shows a schematic diagram of the position of the resonance peak after sample application, the position of the resonance peak shifts to the left (as shown in the fourth curve in fig. 9) after 20 μ l of microRNA-21 solution with the concentration of 100 μ M is dropped on the blank metamaterial (as shown in the first curve in fig. 9), and the position of the resonance peak still does not return to the original blank metamaterial position by using a common cleaning method (absolute ethyl alcohol washing and deionized water washing). After the triple washing, the position of the resonance peak (such as the second curve in fig. 9, i.e. the curve indicated by the long dotted line in the figure) almost coincides with that of the blank metamaterial. The results show that the triple method can effectively remove the sample on the surface of the metamaterial chip, so that the position of the resonance peak of the metamaterial chip after being cleaned is consistent with the blank, and the purpose of repeated use is achieved.
Table 1 shows the position of a resonance peak when a micro RNA-21 sample is repeatedly detected after a metamaterial chip is cleaned by a triple method
From the data shown in table 1, it can be seen that: after 20 mul of microRNA-21 sample with the concentration of 100 mul is detected by using the metamaterial chip, the sample is washed by a triple method, and then the detection steps are repeated for 5 times. The relative offsets of the formants on the metamaterial of the samples measured in 5 times of repetition are respectively as follows: 0.0115THz, 0.0121THz, 0.0117THz, 0.0124THz and 0.0118THz, and the above results are statistically analyzed by variance analysis, the difference has no statistical significance (P >0.05), which indicates that the chip can be reused after the metamaterial chip is cleaned by the triple method.
The embodiments are merely preferred embodiments to fully illustrate the present invention, and the scope of the present invention is not limited thereto. The equivalent substitution or change made by the technical personnel in the technical field on the basis of the invention is all within the protection scope of the invention. The protection scope of the invention is subject to the claims.
Claims (10)
1. A reusable high-flux terahertz metamaterial rapid detection method is characterized by comprising the following steps: the method comprises the following steps:
obtaining an object to be detected and placing the object to be detected on a detection area of the metamaterial chip;
judging whether the diameter of the object to be detected exceeds a preset value, if so, removing solvent water molecules in the object to be detected by adopting a filtering membrane: arranging a filtering membrane matched with the metamaterial chip above the object to be detected, and extruding the object to be detected from top to bottom by the filtering membrane; removing solvent water molecules above the filtering membrane until the object to be detected is deposited on the surface of the metamaterial chip;
if not, adding magnetic beads with the function of a capture probe into the object to be detected, capturing the object to be detected on the surfaces of the magnetic beads, and then separating solvent water molecules of the object to be detected in a magnetic attraction mode under the attraction effect of a magnetic material layer arranged below the metamaterial chip so as to enable the object to be detected to be deposited on the surfaces of the metamaterial chip;
sending the metamaterial chip to a detection instrument to respectively detect objects to be detected in different detection areas;
and (4) until the objects to be detected on all detection areas on the metamaterial chip are detected.
2. The method of claim 1, wherein: further comprising the steps of:
the metamaterial chip after detection is cleaned by adopting a bio-enzyme-SDS-isopropanol triple method, and the method comprises the following specific steps:
placing the metamaterial chip in an SDS solution for soaking, and removing the electrostatic attraction around the magnetic beads and the object to be detected;
washing the surface of the metamaterial chip by using deionized water;
the metamaterial chips were rinsed with isopropanol and blown dry with nitrogen.
3. The method of claim 2, wherein: further comprising the steps of:
the bio-enzyme solution is applied on the surface of the metamaterial chip before soaking with the SDS solution.
4. The method of claim 1, wherein: the filter membrane is used for filtering the substance to be detected with the diameter of 0.5-0.8 μm.
5. The method of claim 1, wherein: the filtration pore diameter arranged on the filtration membrane is 0.22-0.4 μm.
6. The method of claim 1, wherein: the particle size of the magnetic beads is 0.22-1.0 μm.
7. The method of claim 1, wherein: the metamaterial chip is arranged on an object stage by adopting an array moving structure, and the object stage comprises a base;
the base is provided with a positioning groove; the metamaterial chip is movably arranged in the positioning groove;
the metamaterial chip is provided with a plurality of detection areas for placing objects to be detected;
the base is provided with a light hole, and the light hole is matched with a detection area on the metamaterial chip so as to be suitable for the interaction between the terahertz waves and an object to be detected on the detection area of the metamaterial chip; the magnetic material layer is arranged between the positioning groove and the metamaterial chip, so that the metamaterial chip is positioned in the positioning groove through magnetic attraction, the magnetic material layer comprises a first magnetic material layer and a second magnetic material layer, the first magnetic material layer is arranged on the positioning groove, the second magnetic material layer is arranged on the metamaterial chip, and magnetic force can be generated between the first magnetic material layer and the second magnetic material layer.
8. The method of claim 7, wherein: the objective table further comprises a carrier, and the carrier is movably arranged on the base; the metamaterial chip is arranged on the carrier;
a positioning shaft is arranged below the carrier and matched with a groove formed in the base, and the positioning shaft and the groove are movably connected so as to be suitable for interaction between the terahertz waves and the object to be detected on the metamaterial chip detection area.
9. The method of claim 8, wherein: the carrier is a mobile carrier, and the mobile carrier comprises a main body, a to-be-detected part and a detection part; the detection part is arranged at the periphery of the main body, the detection part is arranged in the middle of the main body, a channel for the metamaterial chip to slide is arranged between the detection part and the detection part, and the detection part is right above the light transmission hole so as to be suitable for the interaction between the terahertz waves and the object to be detected on the detection part of the metamaterial chip;
the main part is the circular slab, wait to examine a portion and set up along the circumference, the detection portion sets up in the centre of a circle, the passageway is for setting up the recess between waiting to examine a portion and the detection portion, metamaterial chip and recess cooperation are so that the metamaterial chip can remove on the recess.
10. The method of claim 8, wherein: the detection of the object to be detected in the metamaterial chip human-sending detection instrument is realized according to the following steps:
placing the object stage on an object stage fixing support in the detection instrument;
adjusting a light transmission hole of the objective table to enable the terahertz waves to act on an object to be detected on the detection area of the metamaterial chip;
rotating the carrier on the objective table after the detection of the area to be detected is finished;
adjusting the position of the next detection area of the metamaterial chip on the carrier;
so that the position of the next detection area is right opposite to the light-transmitting hole of the objective table;
until all detection areas on the metamaterial chip are detected.
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